Abstract 6152: Molecular Imaging for Early Detection of Inflammation in Valve Disease
To elucidate the role of angiogenesis in the development and progression of incipient valve disease, we implemented a 6 month, 0.25% cholesterol feeding regimen in NZW rabbits to promote leaflet inflammation and valvular sclerosis that mimicked human disease. Perfluorocarbon (PFC) nanobeacons (~250 nm) targeted specifically to endothelial αvβ3 integrins that are expressed in abundance on valve neovasculature were used to quantify angiogenesis with magnetic resonance molecular imaging (11.7T MRI) and spectroscopy (470 MHz MRS) via detection of the unique 19F spectral signature from bound nanoparticles. 14 rabbits were treated i.v. with 2.2 mL/kg of PFC nanoparticles followed 2 hours later by MRI/MRS of the excised aortic valve leaflets. 19F MRS from valves of rabbits treated with targeted nanoparticles (n=8) exhibited 3.2× greater signal from neovasculature (Figure 1A,B⇓) as compared with nontargeted nanoparticles (n=6; p < 0.001), thus confirming specificity of integrin binding. 19F MRI revealed diffuse involvement of leaflets with angiogenesis, especially at leaflet bases (Figure 1C⇓); and immunocytochemistry confirmed angiogenesis, inflammatory cell infiltration, and lipid and calcium constituents. For the first time, these unique 19F nanobeacon signatures permit background-free, quantitative molecular imaging by MRI/MRS, standing it on par with nuclear imaging yet allowing sufficient anatomic detail to elucidate pathology in tiny structures such as valve leaflets.